Acidosis of hippocampal neurones mediated by a plasmalemmal Ca²⁺/H⁺ pump

Abstract

Modulation of cytosolic calcium ([Ca²⁺]_i) plays a key role in intracellular signalling. In neurones, intracellular Ca²⁺ transients are involved in the regulation of excitability as well as in synaptic transmission and plasticity. Here, we report that depolarization-induced elevation of [Ca²⁺]_i evokes a prominent fall of intracellular pH (pH_i) in voltage-clamped hippocampal pyramidal neurones dialysed with fluorescent indicators of H⁺ and Ca²⁺. This acidification is caused by exchange of internal calcium for extracellular protons via a vanadate-and eosin-sensitive plasmalemmal Ca²VH⁺ pump. In view of the potent neuromodulatory actions of H⁺, these results raise the possibility that changes in excitability and synaptic plasticity, hitherto solely attributed to Ca²⁺ transients, may include a significant component mediated by pH shifts.